Method to manufacture gas monitoring test strips

ABSTRACT

A simple, inexpensive, and versatile device for measuring gaseous substances and a method for manufacture of such devices are described. The device comprises a reflectant backing upon which is disposed a layer which is composed of microparticles coated with a reagent and then with a diffusion layer which contains a diffusion moderator and binder, and optionally a plasticizer. A variety of useful configurations of this device are described.

This application is a continuation of U.S. Ser. No. 07/275,346, filed 23November 1988, now U.S. Pat. No. 4,946,705, which is a divisional ofU.S. Ser. No. 07/043,921, filed 29 April 1987, now abandoned, which is acontinuation-in-part of U.S. Ser. No. 06/644,762 and of U.S. Ser. No.644,761, both filed 27 August 1984 and both now abandoned, whichapplications are continuations-in-part of U.S. Ser. No. 354,497, filed 3March 1982, now abandoned.

TECHNICAL FIELD

This invention relates to the field of measuring exposure to chemicalsubstances and to devices which quantify gaseous substances in theenvironment. More specifically, it relates to simplifying toxic gasdosimetry by integrating means for collection, storage, signaldevelopment and read-out into a single economical device.

BACKGROUND ART

Workers in a variety of environments, such as hospitals, factories andinstitutions of learning may be exposed depending on the circumstancesto a variety of noxious gases at low concentrations. A number of suchcommonly encountered vapors are listed by Saxe, I.N. Dangerousproperties of Industrial Materials, 5th Ed.. Van Nostrand Reinhold Co.,N.Y. (1979) as particular problems in the technologically sophisticatedenvironments of developed countries. Also, lists of hazardous tracesubstances present in work places and in the general environment in theU.S. are published periodically by the Occupational Safety and HealthAdministration and by the Environmental protection Agency in the FederalRegister. Contaminating gases include ethylene oxide, formaldehyde,sulfur dioxide, carbon monoxide, hydrogen sulfide, nitrogen oxides,peroxides, acidic gases, arsine and phosphine, ozone, and halogens. Thislist, of course, is not limiting or all inclusive but includes thosesubstances that may be found in reasonably low concentrations, i.e., inthe ppm or ppb ranges, where prolonged exposure constitutes a hazard.

It is well understood currently that persons in environments where evenpermitted levels of the above gases exist must be monitored forexposure. The time-average concentration or dose applied over time isparticularly important since this parameter correlates strongly with theeffect on the exposed individual. Accordingly, there have been manyattempts to design devices which are capable of assaying total exposureto an individual or to a particular location. Many of these methodsinvolve bulky collection systems such as cartridges providing passagethrough adsorbents such as charcoal or solvents, orcomplex-to-manufacture diffusion devices. See, for example, NIOSH Manualof Analytical Methods, 2nd Ed. Pt 1-NIOSH Monitoring Methods NIOSH77-157-A. and U.S. Pat. Nos. 3,985,017 and 3,924,219. The portableportions of these devices are simply for collection and storage, and theprocedures for signal development and readout require skilled personneland independent instrumentation.

In most instances, the collection device is, in fact, separate from thedetection system. The desired material is extracted from the device, andthe chemistry which permits detection of the target gas by developmentof a color or by other means is performed separately. This generallyinvolves the use of instrumentation with concomitant investment of timeand facilities, capital investment, and commitment of skilled personnel.

The only devices presently commercially available which attempt tointegrate the detection chemistry with the collection device involvecomplex and expensive collector systems attached to development reagentsenclosed in plastic bags. (See U.S. Pat. No. 4,208,371.) The plasticbags are then squeezed into a configuration suitable for reading in acolorimeter. In many cases additional reagents are required which mustbe freshly made in the laboratory. No device currently exists which iscapable of accurately assessing total dosage or time weighted averageexposure at low levels that is simple, inexpensive, and capable ofimmediate quantitative readout by non-expert personnel.

DISCLOSURE OF THE INVENTION

The present invention offers a simple, economical and effective devicefor identifying and quantifying low levels of exposure to environmentalcontaminants, and a simple process for the manufacture of the device.The device can be worn as a badge, attached to equipment or furnishings,or otherwise mounted in the monitored environment. It integratescollection, storage, signal development and readout onto a single,inexpensive article, which requires only contact with a developingsolution and the assistance of a simple reflectance meter to obtainquantitative results.

The device utilizes a reflecting backing material to which is adhered alayer composed of microparticles which are impermeable to the gasanalyte material. The particles are coated with a "collection layer"which includes a behaviorally uniform diffusion layer through which thegas molecules must diffuse in order to reach the microparticle surfaceat which surface lies a reagent for detection. The structure of thetotality of the particle-supported collection layer is such that it hascharacteristics of a true dosimeter, i.e., it responds to time weightedaverage concentration. Accordingly, the diffusion layer is in contactwith a reagent or reagents which is/are coated onto the microparticlesand which is/are specific for the analyte to be measured. The analyte,thus, diffuses through the diffusion layer to the surface of themicroparticles where the reagent system entraps the analyte andpreserves it for future analysis. The trapping reagent is preferably oneof the reagents used in the detecting reaction although a second reagentmay subsequently be added to develop the readable signal. The"collection layer." therefore, is capable of accumulating analyte in atime-dependent manner, so that it becomes a true dosimeter--i.e., itrepresents the integral of (concentration) x (time interval) over acertain exposure time.

Depending on the chemistry of the detecting reaction, it may bedesirable to cover the collection layer with a retractable transparentcover slip which is resistant to ultraviolet light and penetration bycertain gases or the detecting device may be further protected byencasing it in a semipermeable envelope. The cover slip or envelopeserves to protect the collection layer from contamination byparticulates and to provide an enclosed holder for wet reagents so as toprotect the reflectance meter, but, also important, it prevents thealteration of the characteristics of the detection device by water vaporand deterioration of the product of the detecting reaction via light- oroxygen-catalyzed degradation after the detecting reaction is permittedto take place. The detecting reaction may typically be completed bydipping or spraying the device so that the particles contact a solutioncontaining an additional reagent required to form a substance which isperceivable by eye and/or quantifiable by instrumentation.

Thus, in one aspect, the invention relates to a device for quantifyingexposure to-a gaseous substance which device comprises a reflectant,non-porous. Planar backing, and a reflectant, microparticulate adsorbentsupport, upon which microparticulate support is disposed first, acoating of a reagent specifically reactive with analyte, surrounded by adiffusion layer permitting diffusion of the gaseous substance throughit, and which diffusion layer comprises a diffusion moderator, a binder,and, optionally, a plasticizer. In some preferred embodiments, theforegoing device additionally contains a transparent, relativelynon-porous, flexible, planar coverslip attached to the backing, anddisposed flexibly over the microparticles coated with the collectionlayer. This cover slip is permeable to the desired analyte but not tointerfering substances, especially water. Alternatively, the entiredevice is encapsulated in an envelope with these properties.

In other aspects, the invention relates to methods for manufacture ofthe device of the invention, and to methods for measuring the exposureto gaseous substances using this device.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows, diagramatically, a portion of the layer of microparticlesof the device of the invention.

FIG. 2 shows a detection device designed according to prior art devicescontaining microparticles in a sea of collection layer.

FIG. 3 shows the device of FIG. 2 modified by the analyte to be measuredso as to exhibit case II diffusion.

FIG. 4 shows the measuring device represented in FIG. 2 surrounded by acontrolling constant thickness diffusion layer.

FIG. 5 shows the device of the invention having a protective coverslip.

FIG. 6 shows an intermediate stage in the manufacture of the device.

FIG. 7 shows a sample holder for reading the reflectance of the device.

FIG. 8 shows the device having an encapsulating envelope.

MODES OF CARRYING OUT THE INVENTION A. Definitions

As used herein, "quantifying exposure" specifically refers to obtaininga measure of the total dosage for a material which represents theintegral of the product of concentration×time over the series of timesof interest. Thus, since the device "quantifies exposure" it behaves asa true dosimeter. It measures the time weighted average exposure asdefined by the American Conference of Government InternationalHygienists. National Institute of occupational Safety and Health, andthe occupational Safety and Health Administration.

In their definition, a true dosimeter must respond to the integral ∫^(t)_(o) Cdt even for complex variations in concentration of the analyte.For example, if the concentration of the analyte varies with time, theresponse to the true dosimeter will be directly proportional to thisintegral, despite the complexity of the time dependence of theconcentration.

Thus, the device must accumulate response to the gas concentration on acontinuous basis without changing as a result of the total length oftime exposed, or the relative humidity, or other factors which wouldcause deviation of the measured response from being directlyproportional to this integral.

"Reflectant" refers to a property related to the reflection of a lightbeam wherein the ratio of intensity of the reflected beam to that of theincident beam approaches 1. No particular absolute cut-off value suchas, for example 99%, can be given since capacities to reflect representa continuum. Use of this term, therefore, relates to a functionaldefinition where there is sufficient light reflected to accomplish thepurposes of the analysis.

"Non-porous" refers to a substance which does not permit the collectioninto it of gas molecules in substantial amount.

"Collection layer" refers to the coating on the microparticles of thedevice of the invention which exhibits such diffusion, surface andstorage characteristics that it behaves as a true dosimeter. Collectionlayer is used, as will be clear from the context, to refer to thecoating of a single particle or to the totality of such coatings. The"collection layer" on each microparticle has two parts. The reagent atthe surface of the microparticles is capable of trapping the diffusedgas molecules by reaction with the gas. The diffusion layer surroundingthe reagent comprises a diffusion moderator and a binder. The diffusionmoderator and binder are often the same material.

"Diffusion moderator" refers to the component of the diffusion layerwhich controls the uptake of the substance to be measured by creating apatina of constant thickness through which the substance must diffuse.This imparts the characteristic response of a true dosimeter--i.e.,proportional to the integrated product of concentration and exposuretime.

"Specific reagent" refers to a reagent which reacts with the analyte orgas desired to be measured, but with no other substances which arepresent in the environment being assessed and capable of transversingthe diffusion layer. In this sense, "specific reagent" also has afunctional definition--i.e., if reactivity is exclusive to the desiredanalyte in the environment where measurements are to take lace, it issufficiently specific for purposes of the device and methods of theinvention.

"Transparent," like reflectant, has a functional definition. It refersto a material wherein the ratio of intensities of the exit beam to theincident beam approaches 1, but a specific numerical limit ismeaningless. As long as the material is sufficiently transparent topermit the analysis to yield results, it will meet the definition.

"Colored product" refers to a material which absorbs light of selectedwavelengths. It is intended to include both wavelengths resulting in acolor visible to the unaided eye and to the absorption of wavelengthoutside the visible range but amenable to simple instrumentation. Thus"colored product" also refers for example, to materials which absorb inthe near ultraviolet.

"Microparticulate" support refers to particles which are reflectant, andfinely divided so as to expose a large amount of surface area forcoating with collection layers. The size of the particles is inverselyproportional to the sensitivity of the device, since more surface areaimparts more sensitivity to the test. Sizes of particles in the rangecapable of prociding 10-1000 m² /g are suitable for uses in theinvention, but this range is not taken to be limiting. Larger particlesizes are workable but decrease the sensitivity. Smaller particles aredesirable from the standpoint of sensitivity, but may be less convenientto handle. Any workable surface area/mass ratio is within the scope ofthe invention, and the suggested range is merely intended to provideguidance to practitioners thereof.

B. General Description

In general approach, the invention seeks to provide a simple device formeasuring total dosage of a gaseous analyte by providing a diffusionmedium interface with the capacity to entrap molecules of the gas to bemeasured. This diffusion layer is disposed on a reflectant particulatesupport coated with specific reagent and applied to a planar backing sothat the development of a colored product can be quantified using astandard reflectance spectrophotometer. If the colored product is notstable to light or air, or if other materials such as water vaporotherwise distort the results of the test, a coverslip or envelope mayalso be used to protect it.

In practicing the method of the invention using this simplified device(diffusion layer/reagent/microparticulate/backing) the person orlocation to be measured for exposure is provided with the device, andthe reagent at the surface of the microparticles traps the gas duringthe period of exposure.

The manner of entrapment and of progress of the gas toward the reagentis indicated in FIG. 1. As shown in FIG. 1, for the device of theinvention, the gas analyte particles, C, are faced with a constantdiffusion layer thickness in order to reach the reagent. Each additionalC molecule has the same path to travel as the previous one.

This behavior differs from previously constructed devices wherein themicroparticles are distributed in a sea of reagent and a polymercomprising the diffusion layer. As shown in FIG. 2, as time progresses,the reagent at the surface of the sea is used up, and the gas moleculeshave a longer and longer path of diffusion in order to find reagent withwhich they can react. Under these circumstances, as described in U.S.Pat. No. 4,436,819, the response/concentration ratio does not maintainitself over extended time periods, but decreases with the square root oftime.

U.S. Pat. No. 4,436,819 explained how, under certain exceptionalsituations, Case II diffusion could result in a device similar to thatof FIG. 2 acting as a true dosimeter due to continuous swelling of thediffusion moderator in response to the advance at high levels of agaseous penetrant. Under these circumstances, as set forth in U.S. Pat.No. 4,436,819, as time progresses, the gas molecules penetrate theswollen outer layer of the reagent diffusion layer, being limited by adiffusion layer only as they near the location of unused reagent andunswollen diffusion moderator. This is illustrated in FIG. 3 which showsthat the devices comprising particles distributed in a sea ofreagent/binder exhibit true dosimetry only if the effective barrier ofthe sea recedes as rapidly as the zone of consumed reagent. Thus, at anyarbitrary time t, the diffusion layer thickness has not changed. Case IIdiffusion, however, cannot be operative at low penetrant concentrations.Case II diffusion can only be achieved with the devices of FIG. 2 atthese low concentrations by presenting a constant diffusion layerartificially by use of a cover as shown in FIG. 4. In that case, thecover provides a constant penetration requirement while providingreagent in the enclosed binder C. However, this device works only at lowconcentrations which do not use up the surface layer of reagent in theenclosed reagent pad.

Thus, the measurement and absorption of the analyte by the device of thepresent invention depends on the specific configuration wherein aconstant diffusion layer is provided surrounding the reagent-coatedparticles.

When the dosimeter has been exposed for the desired time period, it isremoved from the environment to be monitored and the response measuredin a manner appropriate to the particular gas analyte, the reagentselected, and the configuration of the device. If the device has beenenclosed in an encapsulating envelope, it may need to be removed toeffect color development; the device can then, if desired be replaced inthe envelope. On the other hand, if the device is of the form shown inFIG. 5 and contains a cover slip, the cover slip may automatically belifted when the remainder of the device is placed in contact withsecondary reagent and the slip may then be replaced for readingreflectance for example, in the especially designed carrier of FIG. 7.

Thus the details of the remainder of the procedure depend on :he natureof the particular chemistry employed. In the easiest possible case, if aspecific reagent can be found which results in a detectable product thatis stable over time, no further treatment is necessary. However coloredproducts are notorious for their instability, and the exposure timesrequired by the low levels of analyte are often quite long, thus, morecommonly, the reagent-analyte product is further developed by contactwith a developing solution. In practice, the device is after therequired exposure time conveniently dipped into a solution whichcontains an additional reagent required for the formation of color.Thus, in this case, the reaction takes place in two steps--a specificreagent in the collecting layer stores the analyte in an intermediateform, and one or more reagents in the developing solution convert theintermediate to colored product. In any event, once the colored productis obtained it can be quantified by placing the device in a suitablesample holder so that the intensity of a reflected beam can be comparedwith that of an incident beam.

Such reflectance measuring devices are well known in the art such as theModel 5580 Glucometer (Ames Division. Miles Laboratories) and arecommercially available. In application to this invention, thereflectance meter serves, in effect, to measure the absorbance of lightby the sample at a particular wavelength over a double path lengthtraveled first by the incident and then by the reflected beam throughthe collection layer sample holders for convenient configurations of thedevice of the invention are also commercially available. A holderdesigned to accommodate a rectangular strip particularly useful for thisdevice is shown in FIG. 7. The holder is basically a plastic carrierwhich contains an oblong enclosure 33 for insertion of the device 30. Awindow 32 permits the surface of the device to be exposed to light andreflectance to be measured; the flange 31 permits easy positioning in aninstrument with a cavity into which the department 33 is placed.

The foregoing description is sufficient to describe the features of thedevice when the detectable product is not decomposed by air, byultraviolet light or by removal of solvent, or where interferingsubstances such as water vapor are not present. However, if thedetectable product is unstable, or there are interfering materials inthe test environment it is advantageous to place over the collectionlayer some type of transparent protective cover.

One type of such protection is a cover slip which protects against rapiddiffusion of air, against penetration of ultraviolet light, againstsolvent loss and against the penetration by water vapor. This cover slipmust of course, be transparent in order to be adaptable to the foregoingprocedure. Also, it must be sufficiently flexible so as to permit thedeveloping solvent to make contact with the entire layer of coatedmicroparticles and then prevent air intrusion and solvent loss. Aconvenient configuration to accomplish this is shown in FIG. 5. As shownthere, a transparent cover slip 13 extends over the layer containing thecoated microparticles 12 coated on the backing 11 but is attachedsecurely 10 to the backing. When the device is dipped into a developingsolution, the cover slip separates from the collection layer thuspermitting the solvent to make contact. When it is removed, it can bepressed once again against the layer containing coated particles toprovide the desired protection. The portion of the device containingbacking, layer of particles and cover slip is then placed in a suitablecontainer such as that of FIG. 7 for a reflectance instrument asdescribed above. Whether or not the cover slip is necessary is, ofcourse, entirely dependent upon the chemistry of the detection reaction.

Similarly, the entire device may be encapsulated within a plasticenvelope which is relatively permeable to the contaminant of interestand relatively impermeable to other substances which might interferewith the assay as shown in FIG. 8.

C. Detailed Description of the Device

In general, the device consists of a backing on which are disposedmicroparticles coated at the surface with a reagent and in turnsurrounded by a diffusion layer, and, where made desirable by thechemistry, a cover slip or encapsulating envelope.

Suitable materials for the backing are hard, flat surface relativelythin reflecting polymers such as polystyrene pigmented with TiO₂ orpolyesters which have then extruded into flat sheets. A particularlypreferred backing is a polystyrene-TiO₂ pigmented matte finish backingsuch as that commonly found in graphic art applications.

Bound to the backing are adsorbent, reflectant particles for support,which are coated with a reagent at their surface, in turn surrounded bya diffusion layer which comprises diffusion moderator a binder and,optionally, a plasticizer.

Suitable microparticulate adsorbents ace particulate solids which havesurface areas of at least 10 m² /g, preferably 100-1000 m² /g. Thesematerials usually have a particle size of 100 microns or less, i.e.,0.1-100 microns. Materials which are available in this form includeinorganic refractory oxidic supports, such as alumina, silica, glasstitania, clays and the like, or organic polymers which have been treatedto achieve porosity. e.g., porous cellulose, polypropylene, andpolystyrene-divinylbenzene particles. In order to be compatible with adetection reaction which generates color, the support must beessentially colorless. In addition, these supports can be furthermanipulated chemically so as to change their polarity characteristics.For example, if silica gel is used the hydroxyl groups of the silica canbe derivatized with organic molecules to create a more inert andlipophilic adsorbent.

The reagents used to coat the particles are discussed in a separatesection below.

As to the diffusion moderator and binder virtually all binders arediffusion moderators but not all diffusion moderators are binders. Anyhigh molecular weight material capable of forming a film can serve as adiffusion moderator, therefore this purpose can be served by, forexample, silicone and mineral oils, polyoxyethylenes, and fatty acidesters. These are, however generally not adhesive and do not serve asbinders. Suitable diffusion moderators which can also serve as bindersinclude ether derivatives of cellulose such as, for example,hydroxypropyl or hydroxyethyl cellulose: or ester derivatives such ascellulose acetate, cellulose propionate, or cellulose butyrate. Alsosuitable are mixtures of polyacrylic acid and polyacrylamides, includinghydroxylated polyacrylamides.

Suitable plasticizers include polyethylene glycol (PEG). polypropyleneglycol (PPG) and various phthalate esters such as the dibutyl, ordioctyl esters.

The nature of the specific reagent depends, of course, on the materialto be measured and is discussed in paragraph D below.

In general, the microparticulate support/collection layer containsapproximately 75-80% by weight of the adsorbent support, about 5-15% byweight of diffusion moderator/binder and less than 5% plasticizer.Approximately 10% or less of the support/collecting layer is thespecific reagent. The foregoing percentages and ranges of course, areapproximate and are intended not to be limiting but to indicate thegeneral range of preferred operability. At these ranges individualmicroparticles are coated with collection layer; insufficient weight oflayer materials is present to permit a "sea" in which the particlesfloat. Calculations conducted in connection with designingchromatography supports indicate for example, that a total Weight % ofabout 12% is required for particles of about 200 m² /g and about 24% forparticles of about 400 m² /g. Thus, for the ranges contemplated herein,each particle is surrounded by a collection layer rather than being "atsea".

Where its use is appropriate, the cover slip is composed of a commonlyavailable transparent plastic such as, for example, a thin-layeredpolyester such as 0.005 inch thick polyester materials, for example,Mylar®. Such coverslips are readily available commercially, as they arefrequently used in graphics to encase works of art. Suitable adhesivesfor attaching the coverslip to the reflectant support are alsocommercially available. A particularly preferred adhesive is aproprietary acrylamide-acrylic acid formulation available from 3MCompany as a transfer tape. The adhesive can simply be rolled onto theplastic support from its backing and the tape backing then removed. Theedge of the coverslip is then pressed against the adhesive strip thathas been applied.

When an encapsulating envelope is desirable, a polyethylene orpolypropylene encasement of the entire device may be used as shown inFIG. 8. These materials, for example, are quite permeable to testsubstances such as ethylene oxide, but less so to water, polar materialsand particulates.

D. Specific Reagents and Chemistries

Each gaseous substance desired to be quantified will have acharacteristic specific reagent and associated chemistries appropriateto it. In most cases presently known both a specific reagent and adeveloping reagent are required since the ultimate detection product ischaracteristically less stable than the intermediate formed by reactionof the gas with the specific reagent. However the device is equallyapplicable to chemistries which provide stable detection productsretaining their characteristic light absorption properties over :heperiod of exposure.

Some specific examples of workable chemistries follow:

Ethylene oxide can be detected by reaction with4-(4-nitrobenzyl)pyridine at high PH. The use of this reaction togenerate color when associated with nitrocellulose was disclosed in U.S.Pat. No. 4,094,642. In the device of the present invention, however the4-(4-nitrobenzyl)pyridine is coated onto the microparticles andsurrounded by the diffusion layer at a relatively low PH. Preferablyaround 4. Thus, if this system is used, the support/collection layerwill preferably comprise 10% of the 4-(4-nitrobenzyl) pyridine, 9%hydroxypropylcellulose as diffusion moderator and binder, 3% PEG asplasticizer, and the remainder alumina which has been washed to itsnatural pH of approximately 4. (Silica gel is less advantageous in thisembodiment as its washed surface has a pH which is disadvantageous forthe reaction of the specific reagent (PH 2-3)). No color is developeduntil the ambient pH is modified. Thus, the color is obtained by dippingthe device into a developing solution so that the collecting layercontacts a neutralizing concentration of a suitable base such as, forexample, triethylene tetramine triethylene diamine, ethanolamine orTris. When the color is developed, it can then be read on a reflectancemeter. As the color is known to be decomposed by light and air, thedevice containing the additional coverslip is preferred. Otherwisereading must be made immediately after development.

For measurement of formaldehyde, an operable specific reagent isphenylene diamine adsorbed to the particles supporting the collectinglayer. No color is detectable until the layer is contacted with aperoxide solution, whereupon the intensity of the color formed isdependent on the amount of formaldehyde reacted with the phenylenediamine. In this example, as well, the use of a coverslip is preferred.Another reagent suitable for formaldehyde detection is rosaniline whichforms a colorless complex with the formaldehyde until contacted with SO₂as the secondary reagent.

The chemistries cited above are, of course, merely illustrative.Analytical reagents which form stable colored products with a variety ofother gases, or which form stable intermediates which can be convertedinto colored products are known in the art and available topractitioners.

E. Detailed Description of a preferred Embodiment

A particularly preferred embodiment of the device of the inventionresults in rectangular strips containing at one end a coating of thesupported collection layer and a protecting coverslip secured to thebacking above the supported collection layer by an adhesive. This formof the device is shown in FIG. 5. The rectangular backing, 11, isapproximately 2 inches×1/4 inch and has a layer of coated microparticles12, approximately 1/4 inch square at one end. The backing is apolystyrene-TiO₂ pigmented matte finish strip of 200-500 micronsthickness. The layer 12 is approximately 100-500 microns in depth andcontains 78% alumina particles previously washed to a pH of 4 coatedwith 10% 4(4-nitrobenzyl) pyridine, and then with 3% PEG and 9%hydroxypropyl cellulose. (These percentages represent proportions of thetotal coated particulate mass.) At the amounts of materials given, thealumina particles which are the majority by weight of this mass arecoated thinly with the 4-(4-nitrobenzyl) space pyridine in a single coatand the diffusion layer surrounds the reagent as a thin uniformdiffusion layer around each particle. At these typical amounts, theamount of reagent per square meter is of the order of 10⁻⁴ to 10⁻² g/m²,assuming the particle size range of 10-1000 m² /g of particles.

The supported collecting layer 12 is covered by a coverslip, 13, asshown, which is secured to the backing at 10 by an adhesive. Thecoverslip is 0.005 inch thick polyester and is secured by a strip oftransfer adhesive.

This embodiment can measure concentrations of ethylene oxide over therange of 0.1-5000 ppm over a time range of 10 min-10 hrs. Its totalabsorbing capacity for ethylene oxide is 50 μg. corresponding to anexposure of about 5000 ppm-hr.

The color is developed by contacting the collecting layer with a 1-10%solution of triethylene tetramine by dipping the portion of the stripcovered by the layer of coated particles vertically into the solutionfor 3-5 seconds. The strip is then removed, and the coverslip pressedback into place and wiped with a tissue. The entire sandwich is thenplaced in a reflectance meter using the holder shown in FIG. 7 so thatthe layer shows through the opening 32 and the reflectance read. Thecolor is stable over a period of 10-20 min.

F. Method of Manufacture

The above-described device is most conveniently made by casting onto astrip of backing approximately 5'×4", a stripe lengthwise along thecenter of the backing, the stripe being approximately 1" wide. This canbe done using a suspension of the coated particles in methanol andemploying a commercially available casting machine which rolls thebacking strip through so as to lay down the particulate layer as astripe. FIG. 6 shows the resultant (which has been cut lengthwise inhalf). The backing 21 shows the particulate layer stripe 22. Twoadhesive strips are then applied on either side of the layer stripelengthwise along the backing in approximately the position shown for oneside of the strip at 20 in FIG. 6. The strip is then cut lengthwise inhalf giving two similar lengthwise portions as shown in FIG. 6. Aplastic covering material 23 is applied to the adhesive so that itextends slightly past the end of the collection layer portion of thebacking. The support strip is then cut crosswise as shown in FIG. 6 intoapproximately 1/4 inch sections to give approximately 50 of the devicesshown in FIG. 5 per foot of material. This method of manufacturerepresents a highly efficient manner of constructing a large number ofsuch devices at low cost.

If desired, the device of FIG. 5 may be further enclosed within anenvelope as depicted in FIG. 8 to afford further protection frominterfering substances as described earlier. In such cases. enclosuremay be made at low cost via the use of commercially available automatedpackaging machines such as those manufactured by Circle Design Co. Thecover slip and the envelope are alternative means to protect themicroparticulate layer from contamination, including contamination bywater vapor which is probably the most serious problem encountered indevices of this type. Water vapor is a major contaminant in allenvironments in which personal exposure monitoring is conducted. Forexample, 10% relative humidity equates to more than 5,000 ppm water inthe air, which is a level 5,000 times higher than the maximumpermissible workplace level for ethylene oxide, for example. It is knownthat adsorption of significant quantities of water by collection mediasuch as charcoal, silica, paper, and alumina lower that media's affinityfor the contaminant of interest and may thus change its uptake rateduring measurement. Therefore, any sampling device in order to maintainproper accuracy must take account of this effect. In the devices of theinvention, semipermeable diffusion moderator applied to the reagentparticles and, in some cases, the encapsulating envelope serve as amoisture filter as well as protecting the sampling layer from grossparticulate contamination and, in some instances, the effect of light ofparticular wavelength.

We claim:
 1. A process for manufacturing a test strip useful forquantifying time weighted average exposure to a gaseous substance whichprocess comprises:casting onto the surface of a rectangular sheet ofreflectant, nonporous, planar backing, a layer of reflectant adsorbentmicroparticles wherein said microparticles are coated at their surfacewith a reagent specifically reactive with the gaseous substance to bequantified and wherein said reagent coated particles are further coatedwith a diffusion layer which permits diffusion of the gaseous substancethrough it to contact the specific reagent at the surface.
 2. A teststrip prepared by the process of claim
 1. 3. The test strip of claim 2wherein the diffusion layer comprises a diffusion moderator and abinder, which diffusion moderator and binder may be the same ordifferent.
 4. The test strip of claim 2 wherein the layer ofmicroparticles is 100-500 microns thick.
 5. The test strip of claim 2wherein the microparticles have a surface are of 10-1000 meter² /gram.6. The test strip of claim 5 wherein the microparticles comprise 50-85%of the weight of the particular layer.
 7. The test strip of claim 2wherein the detection reagent is a specific reagent for ethylene oxide.